Cell therapy has been practiced for more than 60 years, starting with the transplantation of “tissue-matched” bone marrow units obtained from bone marrow donors. Additional cell-based therapy options include the collection and transplantation of cord blood units obtained from newborns. Both of these types of cell therapy require the matching of donor cell material with a potential recipient. This is a laborious process and can result in mismatched transplants, endangering the life of the recipient. Other approaches for cell therapy involve collecting cellular material from donors and culturing a single type of cell isolated from those donor materials to produce enough cells that they can be placed in a “bottle” and stored under specialized conditions for use in unrelated recipients. The advantage of the use of allogeneic cells is that they can be stored and are, in theory, available whenever a patient requires a treatment. There are numerous issues with “cells in a bottle”, including the lack of clear cut therapeutic efficacy in humans, the early stage of clinical evaluation of allogeneic products so efficacy has yet to be established, the risks of placing “foreign” DNA in a patient and the possibility of disease transmission. In contrast to all of the foregoing limitations and liabilities, it is possible to obtain a patient's own therapeutic cells (i.e., autologous) while the treatment procedure is on-going and return a concentrated form of the autologous cells to the patient to promote a therapeutic benefit. The invention disclosed herein sets out the approach for providing a combination of autologous cells obtained from two sources of tissue for use at point-of-care (POC), which will have an improved therapeutic outcome compared to the use of cells from a single source of tissue.
The collection of cell populations from multiple tissue depots in the body can be performed in treatment rooms or surgical operating rooms. For example, collecting cells from the bone marrow involves, at least, conscious sedation and localized topical anesthetic at the site of the bone marrow collection. The BMC that is generated in this process contains a variety of types of cells, including hematopoietic stem cells (HSC), mesenchymal stem cells (MSC), endothelial progenitor cells (EPC), stromal cells, and adult cells (including “white” blood cells, megakarocytes, adult platelets, and red blood cells, among others). Collecting cells from a subcutaneous layer (i.e., adipose layer) provides another source of cells, similar in most respects to the preparations obtained from bone marrow, except that there are very few HSCs present, but there is a higher level of MSCs in cell preparations obtained from adipose tissue. Mechanically-released cells found in fluid collected during a traditional liposuction procedure mirror the types of cells obtained when adipose tissue itself is digested with enzymes to release cells. There are many commercial systems and approaches in use for collecting adipose tissue from subcutaneous layers in the human. Manual methods include the syringes and cannulae sold by Tulip Medical Company (CA). A power-assisted liposuction (PAL) system is commercially offered by MicroAire Corp. The PAL system operates by medium frequency oscillations of the suction cannula, which is claimed to provide more uniform fat removal. Another commercial system is available from BodyJet (USA), which involves the use of a jet of water that is capable of “liquefying” the fat tissue prior to removal. All such systems operate with the use of significant levels of vacuum, approximately −21 in Hg. A common feature of all of these approaches is that they result in the collection of both fat tissue and fluid introduced during the procedure.
The claimed invention involves the combination of these two cell types obtained from the same patient during a “single surgical procedure”, thereby providing an advantage to the patient of therapeutic cell preparations from two tissue sources. The combination of cell types affords the patient the best chance of achieving a therapeutic benefit compared to using one or the other cell preparations singly.
In addition to there being some differences in the types of cells present in each of the cell preparations (HSCs in bone marrow, higher frequencies of MSCs in adipose), emerging evidence suggests that potentially the cell preparations are able to function in vivo in unique ways. It has been shown that cultured cell preparations of MSCs from adipose tissue compared to MSCs from bone marrow were better able to recapitulate the bone marrow of radio-ablated recipient mice when the two types of cells were implanted singly into long bone cavities. The data suggests that adipose tissue-derived cells can communicate with HSCs in order to potentiate a therapeutic benefit: faster and more prolific re-capitulation of bone marrow. Consequently, the combination of cells from the bone marrow along with cells from the subcutaneous tissue should provide for an enhanced opportunity for the patient to derive a therapeutic benefit.